The objectives of this supplementary proposal are to amplify our recent design and utilization of neutral acyclic ionophores. We have found that the n-dipropylamides of cis or trans-1,2-cyclohexanedioxydiacetic acid (ETH 45-PR, 47-PR, respectively) show selectivity for cations as follows: Ca ions much greater than Sr ions greater than H ions Ba ions greater than Na ion greater than NH4 ion, Li ion greater than K ion, Mg ion, Rb ion, i.e. they are selective for calcium chelation. The selectivity factor (via EMF measurements using the ligands as substrates in membrane electrodes) for our best ligand, 45-PR for Ca/Na is ca. 50:1. We hope to improve this ratio and increase the calcium selectivity generally, thus making the system even more attractive for use in biological systems depending on selective calcium chelation and transport. The various factors influencing divalent vs. monovalent cation selectivity are reviewed. Specific new approaches to the synthesis of potential ligands are given. The incorporation of 3-4 chelating chains (instead of the two chains currently used), the use of molecules which form a flexible cavity by hydrogen-bonding between phenolic and carboxylic groups, and polymer-bound ligands are stressed. The compounds will be tested for ionophore and chelation ability by several methods including ultraviolet spectral changes, conductivity changes, the isolation of crystal-line complexes of determinable stoichiometry, and nmr studies. The more promising ligands will be tested for ion-transport properties, as substrates in ion-selective electrodes by Professor Wilhelm Simon (ETH, Zurich) and for heart muscle contraction activity and regulation properties by Professor Arnold Schwartz, Baylor University, College of Medicine.